MOLECULAR ASPECTS OF ALCOHOL METABOLISM: Transcription Factors Involved in Early Ethanol-Induced Liver Injury

2004 ◽  
Vol 24 (1) ◽  
pp. 55-78 ◽  
Author(s):  
Laura E. Nagy
Keyword(s):  
Transcription Factors ◽  
Liver Injury ◽  
Alcohol Metabolism ◽  
Molecular Aspects

scholarly journals Immune-Mediated Drug-Induced Liver Injury: Immunogenetics and Experimental Models

2021 ◽  
Vol 22 (9) ◽  
pp. 4557
Author(s):  
Alessio Gerussi ◽  
Ambra Natalini ◽  
Fabrizio Antonangeli ◽  
Clara Mancuso ◽  
Elisa Agostinetto ◽  
...  
Keyword(s):  
Liver Injury ◽  
Experimental Models ◽  
Clinical Event ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
Immune Mediated ◽  
Liver Injuries ◽  
Immunological Mechanisms ◽  
Molecular Aspects ◽  
Therapeutic Tools

Drug-induced liver injury (DILI) is a challenging clinical event in medicine, particularly because of its ability to present with a variety of phenotypes including that of autoimmune hepatitis or other immune mediated liver injuries. Limited diagnostic and therapeutic tools are available, mostly because its pathogenesis has remained poorly understood for decades. The recent scientific and technological advancements in genomics and immunology are paving the way for a better understanding of the molecular aspects of DILI. This review provides an updated overview of the genetic predisposition and immunological mechanisms behind the pathogenesis of DILI and presents the state-of-the-art experimental models to study DILI at the pre-clinical level.

scholarly journals Schisantherin A alleviated alcohol-induced liver injury by the regulation of alcohol metabolism and NF-kB pathway

2018 ◽  
Vol 67 (4) ◽  
pp. 451-461 ◽  
Author(s):  
Bin Li ◽  
Dongnan Li ◽  
Yuehua Wang ◽  
Xianjun Meng ◽  
Xiyun Sun ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alcohol Metabolism ◽  
Schisantherin A

scholarly journals AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma

2020 ◽  
Vol 4 (17) ◽  
pp. 4151-4164
Author(s):  
Timon A. Bloedjes ◽  
Guus de Wilde ◽  
Chiel Maas ◽  
Eric Eldering ◽  
Richard J. Bende ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Transcription Factors ◽  
Glycogen Synthase ◽  
Gene Activation ◽  
Prognostic Significance ◽  
Myeloid Cell ◽  
Akt Signaling ◽  
Cycle Arrest ◽  
Foxo Transcription Factors ◽  
Molecular Aspects

Abstract The phosphatidylinositide-3 kinases and the downstream mediator AKT drive survival and proliferation of multiple myeloma (MM) cells. AKT signaling is active in MM and has pleiotropic effects; however, the key molecular aspects of AKT dependency in MM are not fully clear. Among the various downstream AKT targets are the Forkhead box O (FOXO) transcription factors (TFs) and glycogen synthase kinase 3 (GSK3), which are negatively regulated by AKT signaling. Here we show that abrogation of AKT signaling in MM cells provokes cell death and cell cycle arrest, which crucially depends on both FOXO TFs and GSK3. Based on gene expression profiling, we defined a FOXO-repressed gene set that has prognostic significance in a large cohort of patients with MM, indicating that AKT-mediated gene activation is associated with inferior overall survival. We further show that AKT signaling stabilizes the antiapoptotic myeloid cell leukemia 1 (MCL1) protein by inhibiting FOXO- and GSK3-mediated MCL1 turnover. In concordance, abrogation of AKT signaling greatly sensitized MM cells for an MCL1-targeting BH3-mimetic, which is currently in clinical development. Taken together, our results indicate that AKT activity is required to restrain the tumor-suppressive functions of FOXO and GSK3, thereby stabilizing the antiapoptotic protein MCL1 in MM. These novel insights into the role of AKT in MM pathogenesis and MCL1 regulation provide opportunities to improve targeted therapy for patients with MM.

Fructose 1, 6-diphosphate prevents alcohol-induced liver injury through inhibiting oxidative stress and promoting alcohol metabolism in mice

2017 ◽  
Vol 815 ◽  
pp. 274-281 ◽  
Author(s):  
Ling Li ◽  
Yifei Wu ◽  
Fangyuan Yin ◽  
Qin Feng ◽  
Xiaoliang Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Alcohol Metabolism

scholarly journals Lipopolysaccharide Stimulates p62-Dependent Autophagy-Like Aggregate Clearance in Hepatocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Christine Chen ◽  
Meihong Deng ◽  
Qian Sun ◽  
Patricia Loughran ◽  
Timothy R. Billiar ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Liver Injury ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Energy Homeostasis ◽  
Misfolded Proteins ◽  
Wild Type ◽  
Cell Lysates ◽  
Lc3 Puncta ◽  
Tlr4 Activation

Impairment of autophagy has been associated with liver injury. TLR4-stimulation by LPS upregulates autophagy in hepatocytes, although the signaling pathways involved remain elusive. The objective of this study was to determine the signaling pathway leading to LPS-stimulated autophagy in hepatocytes. Cell lysates from livers of wild type (WT; C57BL/6) mice given LPS (5 mg/kg-IP) and hepatocytes from WT, TLR4ko, and MyD88ko mice treated with LPS (100 ng/mL) up to 24 h were collected. LC3II, p62/SQSTM1, Nrf2, and beclin1 levels were determined by immunoblot, immunofluorescence, and qPCR. Autophagy-like activation was measured by GFP-LC3-puncta formation and LC3II-expression. Beclin1, Nrf2, p62, MyD88, and TIRAP were knocked-down using siRNA. LC3II-expression increased in both liver and hepatocytes after LPS and was dependent on TLR4. Beclin1 expression did not increase after LPS in hepatocytes and beclin1-knockdown did not affect LC3II levels. In hepatocytes given LPS, expression of p62 increased and p62 colocalized with LC3. p62-knockdown prevented LC3II puncta formation. LPS-induced LC3II/p62-puncta also required MyD88/TIRAP signaling and localization of both Nrf2 and NFκB transcription factors to the nucleus to upregulate p62-expression. Therefore, TLR4-activation by LPS in hepatocytes induces a p62-mediated, not beclin1-mediated, autophagy-like clearance pathway that is hepatoprotective by clearing aggregate-prone or misfolded proteins from the cytosol and preserving energy homeostasis under stress.

Regulation of gene expression by hypoxia

2008 ◽  
Vol 414 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Niall Steven Kenneth ◽  
Sonia Rocha
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Cellular Response ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Hypoxia Inducible Factor ◽  
Translation Regulation ◽  
Cellular Gene ◽  
Cellular Pathways ◽  
Molecular Aspects

Hypoxia induces profound changes in the cellular gene expression profile. The discovery of a major transcription factor family activated by hypoxia, HIF (hypoxia-inducible factor), and the factors that contribute to HIF regulation have greatly enhanced our knowledge of the molecular aspects of the hypoxic response. However, in addition to HIF, other transcription factors and cellular pathways are activated by exposure to reduced oxygen. In the present review, we summarize the current knowledge of how additional hypoxia-responsive transcription factors integrate with HIF and how other cellular pathways such as chromatin remodelling, translation regulation and microRNA induction, contribute to the co-ordinated cellular response observed following hypoxic stress.

scholarly journals Herb-Induced Liver Injury Related to Reynoutria multiflora (Thunb.) Moldenke: Risk Factors, Molecular and Mechanistic Specifics

2021 ◽  
Vol 12 ◽  
Author(s):  
Xing-Ran Zhai ◽  
Zheng-Sheng Zou ◽  
Jia-Bo Wang ◽  
Xiao-He Xiao
Keyword(s):  
Risk Factors ◽  
Herbal Medicine ◽  
Liver Injury ◽  
Clinical Characteristics ◽  
Molecular Mechanisms ◽  
Basic Research ◽  
Polygonum Multiflorum ◽  
The West ◽  
The World ◽  
Molecular Aspects

Herbal medicine is widely used in Asia as well as the west. Hepatotoxicity is one of the most severe side effects of herbal medicine which is an increasing concern around the world. Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb., PM) is the most common herb that can cause herb-induced liver injury (HILI). The recent scientific and technological advancements in clinical and basic research are paving the way for a better understanding of the molecular aspects of PM-related HILI (PM-HILI). This review provides an updated overview of the clinical characteristics, predisposing factors, hepatotoxic components, and molecular mechanisms of PM-HILI. It can also aid in a better understanding of HILI and help in further research on the same.

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